Interferons have great potential as drugs for the treatment of a variety disease states, e.g. various types of viral infections and certain cancers.
As used herein, the term "interferon" includes natural and recombinant alpha (leucocyte) and beta (fibroblast) interferons, but alpha interferons are preferred. As used herein, the term "alpha interferon" means a natural or recombinant interferon exhibiting biological properties similar to those of human leucocyte interferon. It should be noted that a number of alpha interferon species are known, usually designated by a numeral after the Greek letter, and all are contemplated for use in this invention. Also included within the scope of this invention are the so-called alpha hybrid interferons wherein fragments of two or more native alpha interferon species are joined (see for instance, EP No. 51873). Preferred forms of alpha interferon for use in the formulations of the present invention are alpha-1 and alpha-2 interferon. Particularly preferred for use in the formulations of the present invention is alpha-2 interferon. Alpha-2 interferon may be prepared by recombinant-DNA methods, for example those disclosed by Nagata et al., Nature, Vol. 284, pages 316-320 (1980), and by Weissmann, European Patent No. 32,134.
Biologically stable interferon compositions are known. See Kwan U.S. Pat. No. 4,496,537, herein incorporated by reference, which claims a method of improving biological stability of an interferon formulation comprising the addition of glycine or alanine to an alpha interferon formulation prior to lyophilization. While such lyophilized powders are not generally susceptible to microbiological contamination since interferon formulations are commonly prepared under aseptic conditions, reconstituted solutions of these lyophilized formulations are susceptible to microbiological contamination and growth. This makes reconstituted solutions unsuitable for multiple dose applications, e.g. nasal or ophthalmic applications, where the solution will not be used all at once.
Various preservatives and preservative combinations have been tested, but in general have been found to cause physical instability such as precipitation or turbidity in the reconstituted solution. Some preservatives are also ineffective in preventing microbial contamination and/or reduce interferon activity.